Multifocal motor neuropathy mimicking motor neuron disease: nine cases

Journal of the Neurological Sciences, 1-2, 169, pages 76 - 79

Abstract

Multifocal motor neuropathy with persistent conduction block (MMN) is a rare clinical entity, mimicking motor neuron disease (MND). In order to research which are the most frequent nerves and segments where conduction block (CB) can be identified, we reviewed the clinical and neurophysiological data of nine patients with MMN who were studied and followed by the authors. Weakness and muscle atrophy of the dominant hand was the most frequent presentation. Lower limbs were involved later in the disease evolution. The ulnar and median nerves were the most affected nerves. They had conduction blocks mostly at the forearm and at Erb’s point–elbow (or above elbow) segments. Both common peroneal and tibial nerves were frequently affected at their distal segments, but proximal segments were also probably involved. The presence of anti-GM1 antibodies was variable, and their determination was not essential for the diagnosis of MMN. Eight patients given IV immunoglobulin therapy had no disease progression. One patient was responsive to corticosteroids. The CB identification in our patients allowed us to clearly distinguish MMN from MND. The good prognosis and need for management with IV immunoglobulin, support the crucial role of a careful neurophysiological study to diagnose this clinical entity.

Keywords: Motor neuropathy, Conduction block, ALS.

1. Introduction

Multifocal motor neuropathy with persistent conduction block (MMN) is a rare clinical entity, identified in the early eighties. Motor neuropathy with conduction block was initially described as a variant of chronic acquired demyelinating polyneuropathy [1] . A pure motor neuropathy with conduction block was later described in patients who had a clinical picture mimicking motor neuron disease (MND) [2] and [3]. Recently, a few series were published with a larger number of patients [4] and [5].

Because the differential diagnosis between MMN and MND depends on a careful neurophysiological investigation, it seems appropriate to evaluate which are the most frequent nerves and segments where conduction block can be identified. In order to clarify this point, we reviewed the clinical and neurophysiological data of nine patients with MMN who were studied and followed by the authors.

2. Population and methods

From 1991 to 1997 we selected all the patients with the diagnosis of MMN made in our EMG laboratory. The patients were referred to us for clinical and neurophysiological evaluation with the diagnosis of MND or motor neuropathy with liability to pressure palsies. Our population of MMN included seven males and two females with a mean age of 44 years, ranging from 27 to 66, and a mean duration of symptomatic disease of 4.9 years (ranging from 0.25 to 15) at the time of neurophysiological investigation. None of our patients had a familial history of neurological disorder or diabetes.

Investigation included motor nerve conduction study (with F waves) of ulnar, median, peroneus and tibialis nerves. Ulnar nerve was stimulated at wrist, below elbow, above elbow, axilla and Erb’s point. Median nerve was stimulated at wrist, elbow, axilla and Erb’s point. Peroneal nerve was stimulated at ankle, below and above fibula. Tibial nerve was stimulated at ankle and at popliteal fossa. Supramaximal stimulation was applied by a bipolar electrode. A monopolar stimulating electrode was used to confirm conduction block (CB), if necessary, at Erb’s point or popliteal fossa. Stimulus duration was set at 0.2 ms, but at proximal sites and for the ulnar nerve at the below elbow site a longer duration was used in some cases. The responses were recorded through surface electrodes (Ag/AgCl) using a belly–tendon montage and filtered using a setting of 20 Hz–10 KHz. In patients with weak wrist extensors the motor fibres of the radial nerve were also investigated. The radial nerve was stimulated at arm, axilla and Erb’s point. The responses were recorded by a needle electrode inserted in extensor digitorum communis and extensor indicis, to minimize volume conducted potentials from muscles nearby.

The sensory potentials of the following nerves were analysed in all patients: median (wrist-digit III), ulnar (wrist-digit V), sural (sural-ankle), bilaterally. In patients in whom the motor fibres of the radial nerve were investigated, its sensory potential (distal forearm–digit I) was also obtained. Sensory potentials were recorded antidromically with surface electrodes.

Conduction block (CB) was defined as more than 50% reduction in both amplitude and the negative-peak area on proximal stimulation, as compared to the distal stimulated response, with no more than a 15% change in the negative peak duration [6] . In cases with a marked reduction of the amplitude of the motor response, abnormality of F waves and weakness in a nerve territory, conduction block was considered probable (PCB).

Inclusion criteria in this study were:

  • 1. The presence of CB located in areas not prone to compression in two or more motor nerves.
  • 2. Normal motor and sensory conduction study.

3. Results

All of our patients had unilateral hand weakness as the first symptom (the right hand in eight). In one patient, right hand weakness was quickly followed by right foot droop.

At the time of neurophysiological investigation three patients had isolated right hand weakness, the others had unilateral (two) or bilateral (three) upper limb involvement associated with at least one lower limb paresis. No patient had involvement of muscles innervated by cranial nerves nor sensory signs. Tendon reflexes were usually abolished or reduced in affected regions but one patient had diffuse brisk reflexes. The plantar responses were flexor in seven patients and unilaterally suspicious in one case. Concerning territory distribution, in our observation nine median, nine ulnar, two radial, five peroneal and six tibial nerves were clinically affected. The seven patients with marked muscular atrophy had longer disease duration (6.1 years) as compared with those with no atrophy (0.6 years). All patients were referred with the diagnosis of motor neuron disease, but the alternative diagnosis of neuropathy with liability to pressure palsies was raised in two patients, in spite of the fact that none of them had familial history of this disease. Clinical features at the time of the EMG investigation are summarised in Table 1 .

Table 1 Clinical features at the time of the EMG study

Clinical features Number of patients
Isolated right hand weakness 3
Distal right hemiparesis 1
Distal right hemiparesis+left foot drop 3
Distal right hemiparesis+left hand weakness 1
Distal left hemiparesis+right hand weakness 1

Protein electrophoresis and immunoelectrophoresis showed an increased monoclonal IgM band in one patient. In five patients anti-GM1 ganglioside antibodies were sought by ELISA technique. In two, low titres of IgM anti-GM1 (>1/200 and >1/500) were identified. The CSF protein content was increased in one patient only (1 g/l).

EMG results are summarised in Table 2 . In one patient, CB criteria for the right ulnar nerve was only observed by recording the response at the first dorsal interosseous whereas the response recorded at ADM had a low amplitude but did not show a 50% decrement ( Fig. 1 ). All sensory potentials had normal values.

Table 2 Nerves and sites with conduction blocks a

Nerves CB PCB
W–E E–Ax Ax–Erb’s A–F A–P
Median 8 2 0
Ulnar 6 2 4 0
Radial 0 2
Peroneal 6 6 1
Tibial 3 3 4

a CB: conduction block; PCB: probable conduction block; W–E: segment wrist–elbow for median nerve and wrist–below elbow for ulnar nerve; E–Ax: segment elbow–axilla for median nerve and above elbow–axilla for ulnar nerve; A–F: segment ankle–below fibula for peroneal nerve; A–P: segment ankle–popliteal fossa for tibialis nerve.

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Fig. 1 (A) Right ulnar nerve investigation, recording the response from the abductor digiti minimi (ADM). The amplitude and area decrement in the most proximal segment was not enough to accept a partial conduction block. (B) Recording the response from the first dorsal interosseous (which was weaker than the ADM) a partial conduction block was identified in the most proximal segment.

Eight patients were treated with human immunoglobulin (HIG) in doses of 400 mg/kg/day for 5 days initially with monthly treatments of the same dosage for 1–2 days. Two patients had functional recovery after 3–4 months of treatment, in one patient a decrement of CB block was observed in one nerve. Three patients had no progression but did not improve. Two patients died, one in an automobile accident and another, who had an IgM monoclonal band on immunoelectrophoresis, developed a fatal B cell lymphoma two months after our neurophysiological investigation. One patient was lost for follow-up.

One patient, fulfilling the clinical and EMG criteria for MMN, improved with corticosteroids and became dependent on low-doses of corticosteroids. This patient has been described previously [7] .

4. Discussion

We have studied nine patients with MMN. No patient had bulbar or sensory abnormalities. In one patient brisk reflexes and unilateral dubious plantar response raised the suspicion of amyotrophic lateral sclerosis. The other patients were referred with the diagnosis of MND with pure lower motor neuron signs or liability to pressure palsies. Mononeuropathy multiplex was not largely considered as an initial diagnosis probably because of either the absence of sensory impairment or pain. Weakness and muscle atrophy of the dominant hand was the most frequent presentation. Muscle atrophy was generally observed in cases with a longer duration of disease. Lower limbs are more involved later in the disease evolution. In our clinical observation paresis in nerve trunk territory was a striking clinical feature. The nerves most affected were the ulnar and median nerves. There was conduction block mostly in the forearm and the Erb’s point-elbow (or above elbow)-segment, probably because these are the longest segments investigated. The radial nerve is more difficult to investigate but possibly is not so affected as those nerves described above. Both peroneal and tibial nerves were frequently affected in their distal segments. In spite of being technically difficult to confirm, proximal segments are also frequently involved, particularly at the tibial nerve. It might be very useful to test for conduction block in one nerve recording the motor response in more than one target muscle, as shown in one of our cases, because the motor fibres for different muscles in one nerve can be differentially affected ( Fig. 1 ).

Laboratory investigation showed that the presence of anti-GM1 antibodies was inconstant, and their determination is not essential to diagnose this neuropathy [4] . As described by others in this disease [5] , one of our patients had an increased protein content in the CSF. Interestingly this patient had a neuropathy responsive to corticosteroids, in spite of having a pure motor neuropathy with criteria for partial conduction block and normal sensory conduction in those abnormal segments [7] . We believe this patient represents a transition between MMN and chronic inflammatory demyelinating neuropathy. Another of our patients, who had an IgM monoclonal band, developed a B-cell lymphoma which caused his death. MMN can occur in association with immunological disorders [8] which should be sought, as shown in our case.

Patients submitted to immunoglobulin therapy had generally no disease progression, but the optimal treatment regimen is still to be defined. Muscles with a severe weakness and atrophy are most resistant to treatment [4] .

In our patients CB identification allowed us to clearly distinguish MMN from MND. Immunoglobulin therapy should be tried in these patients, however those with a longer evolution time and more marked muscle atrophy are the least responsive. An early identification of this condition is important to treatment success.

Acknowledgments

We are grateful to Ms Victoria Ribeiro for technical assistance and Ms Margarida Fernandes for secretarial support.

References

  • [1] R.A. Lewis, A.J. Sumner, M.J. Brown, A.K. Asbury. Multifocal demyelinating neuropathy with persistent conduction block. Neurology. 1982;32:958-964
  • [2] G.J. Parry, S. Clarke. Multifocal acquired demyelinating neuropathy masquerading as motor neuron disease. Muscle Nerve. 1988;11:103-107 Crossref
  • [3] A. Pestronk, D.R. Cornblath, A.A. Ilyas, H. Baba, R.H. Quarles, J.W. Griffin, et al. A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside. Ann. Neurol.. 1988;24:73-78 Crossref
  • [4] P. Bouche, A. Moulonguet, A.B. Younes-Chennoufi, D. Adams, N. Baumann, V. Meininger, et al. Multifocal motor neuropathy with conduction block: a study of 24 patients. J. Neurol. Neurosurg. Psychiatry.. 1995;59:38-44 Crossref
  • [5] N. Forestier, B. Chassande, A. Moulonguet, T. Maisonobe, S. Schaeffer, N. Birouk, et al. Neuropathies motrices multifocales avec blocs de conduction. Rev. Neurol. (Paris). 1997;153:79-586
  • [6] G.J. Parry. Motor neuropathy with multifocal conduction block. P.J. Dyck, P.K. Thomas, J.W. Griffin, P.A. Low, J.F. Poduslo (Eds.) Peripheral neuropathy 3rd ed (Saunders, Philadelphia, 1993) 1518-1524
  • [7] M. de Carvalho, M.L. Sales-Luı́s. Relapsing chronic corticosteroid-responsive multifocal motor neuropathy with conduction block. Electromyogr. Clin. Neurophysiol.. 1997;37:95-97
  • [8] P.W. Jamieson, M.J. Giuliani, A.J. Martinez. Necrotizing angiopathy presenting with multifocal conduction blocks. Neurology. 1991;41:442-444

Footnotes

a Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal

b Department of Neurology, EMG laboratory of Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal

* Corresponding author. Tel.: +351-1-797-7782; fax: +351-1-795-7474